Uppers, Downers, All Arounders: Chapter 2

What happens when the "stop" switch is flipped, and in what cases does it fail?

"Stop" switch shuts down the "go" switch and the "do it again" message ceases. Signals the cells to stop releasing dopamine. The "stop" switch malfunctions when substance abusers have altered their brain chemistry, and the "go" switch is more powerful than usual. When that happens, there is nothing that is stopping the craving so the person continues use because there are no instructions to stop.

Basics of Orbital Prefrontal Cortex and STOP switch:

- Consist mainly of the orbital prefrontal cortex along with the fasciculus retroflexus (FR) and the lateral habenula. - One conduit of communication that gets damaged is the fasciculus retroflexus. In an addicted brain, the "stop" messages never reach the old brain. - Another mechanism is the lateral Habenula and is located in the old brain. It is triggered by the FR and normally shuts off the "go" switch by limiting the release of dopamine.

Routes of Administration: Mucous Membrane Absorption

- Insufflation: Snorted into the nose. Faster than oral ingestion. - Sublingually/Buccally: Absorbed through mucous membranes under the tongue (sublingually) or absorbed between the gums and cheek (Buccally). 3-5 minutes for effects to begin. - Anal: absorbed through tissues lining the rectum or vagina. 10-15 minutes for effects to begin.

Routes of Administration: Injection

- Intravenously: directly into the bloodstream by way of a vein. - Intramuscularly: into a muscle mass. - Subcutaneously: under the skin. Main disadvantage is that injecting is the most dangerous method of use because it bypasses the bodies natural defenses exposing the user to viruses and infections.

Basics of Nucleus Accumbens (NAc) Septi and GO switch:

- It is a powerful motivator (reinforcer). It gives mammals certain feelings that drive them to actions that primarily ensure their continued survival. - Direct brain stimulation of this nuclei had a more powerful influence on behavior. - Psychoactive drugs that result in addiction stimulate the NAc as powerfully if not more than does direct electrical stimulation.

Three theories about how psychoactive drugs affect the "go" and "stop" switches of the addiction pathway:

1. There is no satiation point. 2. Signals from the "go" and "stop" switches are willfully ignored. 3. Psychoactive substances disrupt communications between the "stop" and "go" switches.

The "go" switch does these three things when it is activated:

1.) It tells us what we are doing is necessary for survival. 2.) The "go" switch also tells us to remember what we did to survive. 3.) Then it tells us, "whatever you did, do it over and over again until you are satisfied; it is necessary for your survival".

Old Brain: 3 Main Functions

1.) Regulates physiological functions of the body such as respiration, heartbeat, temperature, hormone release, etc. 2.) Experiencing basic emotions and cravings such as anger, fear, hunger, thirst, etc. 3.) Imprinting survival memories such as "that green plant tastes good", "this bad odor signifies danger", etc.

How long, in half-lives, does it take for a drug to become undetectable in most drug tests?

2.5 hours

What are some of the ways in which drugs reach the blood?

A drug can be carried within blood cells, in the plasma outside the cells or it could also travel on protein molecules.

What is Coca-ethylene?

A metabolite of cocaine that is formed when alcohol and cocaine are used together.

Briefly summarize the ideas on neurotransmitters and receptor sites:

A neurotransmitter is designed to bind with a compatible receptor site. Each nerve cell produces and sends only one type of neurotransmitter. A single nerve cell can have receptors for several thousand different types of neurotransmitters, and it can have thousands of receptors.

Type of Tolerance: Inverse Tolerance

A person becomes more sensitive to the effects of a drug.

Polydrug Abuse: Replacement

A user will use another drug when their desired drug is not available or if they are looking for something less harmful than their drug of choice.

New Brain: Definition

Also called the neocortex, processes information coming from the old brain, from different areas of the brain and from the sense via the peripheral nervous system.

What happens with an excess of psychoactive drugs?

Alters the user's perception of messages coming from the external environment.

Neurotransmitters and Function: Amino Acids - Glutamate

An important excitatory neurotransmitter, is present in 80% of neurons in the brain. Enhances the prominence of dopamine's effects when it is released in response to psychoactive drugs. Also important in memory reinforcement.

How does emotional state affect drug metabolism?

Anxiety, anger, and other emotions can exaggerate the effects.

Type of Tolerance: Cross Tolerance

As a person develops tolerance to one drug, they can develop tolerance to other drugs

Why are emotionally charged memories more deeply imprinted than everyday memories?

Because more dendritic spines are created from those events and they are much larger than those created from average sensory input.

Drug Processes that Alter Effects of Neurotransmitters: Block Neurotransmitter Release

Blocks the release of neurotransmitters from the vesicles.

Type of Tolerance: Dispositional Tolerance

Body speeds up the breakdown (metabolism) of a drug.

Type of Tolerance: Acute Tolerance

Brain and the body begin to adapt almost instantly.

Type of Tolerance: Behavioral Tolerance

Brain learns to compensate for the effects of a drug.

Building Blocks of Nervous System: Axon

Carries the message from the cell body to the terminals

Important Processes That Give Clues for Addiction and Relapse: Epigenetic Changes

Changes in synapses and in parts of the brain and the body are due to alternative instructions given to the genes.

Polydrug Abuse: Mixing

Combining drugs to induce different effects.

How are messages between neurons sent and received? Inhibitory Neurotransmitters:

Decrease cell firings.

Define: Drug Distribution:

Delivery of the medication from the site of administration to the various organs in the body through body fluids, primarily the blood.

Psychological Dependence: Positive Reinforcement

Desire for the positive effects of a psychoactive substance.

Psychological Dependence: Negative Reinforcement

Desire to avoid the negative effects or emotions of abstinence.

How does race affect drug metabolism?

Different ethnic groups have different types of enzymes.

Neurotransmitters and Function: Monoamines - Dopamine

Discovered in 1958. Helps regulate fine motor muscular activity, emotional stability, satiation, and the addiction pathway. Dopamine is the most crucial neurotransmitter involved in both substance and process addictions.

Neurotransmitters and Function: Others - Anandamide and endocannabinoids

Discovered in 1995. Activate two receptor sites in the body, CB1 and CB2, which are found in variety of locations within and outside the central nervous system. In the CNS, the receptors are in the limbic system and in areas responsible for integration of sensory experiences with emotions as well as those controlling learning, motor coordination and memory. Endocannabinoids can act as analgesic or pain reliever.

Routes of Administration: Oral Ingestion

Drug passes through the esophagus and the stomach to small intestine, where it is absorbed into capillaries enmeshed in the intestinal walls. Effects are delayed 20-30 minutes.

Routes of Administration: Contact Absorption

Drug saturated adhesive patches that are applied to the skin and allows measured quantities of a drug to be passively absorbed for up to seven days. It is noninvasive transdermal absorption that can take 1-2 days for effects to begin.

Baisc Idea: Agonist drugs

Drugs that bind to receptors and mimic or facilitate the effects of neurotransmitters.

Baisc Idea: Partial agonists

Drugs that bind to receptors and partially mimic the effects of neurotransmitters.

Baisc Idea: Inverse agonists

Drugs that bind to receptors and stabilize the receptor in its inactive state by hyperpolarizing it so that it cannot react.

Baisc Idea: Antagonist drugs

Drugs that bind to receptors but don't activate them and thereby block neurotransmitters

Define: Drug Synergism

Exaggeration of effects when two or more drugs are taken together

Withdrawal: Purposive

False portrayal of severe withdrawal symptoms by an addict to manipulate a physician or pharmacist into providing drugs to manage symptoms.

Neurotransmitters and Function: Others - Acetylcholine

First neurotransmitter discovered (1914). Mostly active at nerve/muscle junctions. Helps induce REM sleep and modulate mental acuity, memory, and learning.

Withdrawal: Protracted

Flashback or recurrence of the addiction withdrawal symptoms. Often causes recovering addicts to slip, or renew their drug use, ultimately leading to relapse.

Drug Processes that Alter Effects of Neurotransmitters: Force Neurotransmitter Release

Force the release of neurotransmitters by entering the presynaptic neurons, causing more to be released than occur naturally.

Neurotransmitters and Function: Opioid Peptides - Substance P

Found in sensory neurons. Conveys pain impulses from the peripheral nervous system back to the central nervous system. Enkephalins block the release of substance P, thereby subduing pain.

Neurotransmitters and Function: Monoamines - Norepinephrine

Function as stimulants when activated by a demand from the body for energy, particularly when the fight or flight response is activated. Stimulate the autonomic system and affect motivation, hunger, attention span, confidence and alertness.

Neurotransmitters and Function: Others - Adenosine

Functions as autoregulatory local hormone. Most cells contain adenosine receptors that when activated, inhibit some cell functions. Adenosine has an inhibitory effect on the CNS.

Neurotransmitters and Function: Amino Acids-GABA

Gama Amino Butyric Acid is the brains main inhibitory neurotransmitter and is involved in 25-40% of all synapses in the brain. It controls impulses, muscle relaxation, and arousal and generally slows down the brain.

Neurotransmitters and Function: Others - Nitric Oxide

Gas involved in message transmission to the intestine and other organs. Also plays a part in Regulating emotions. Nitric oxide is not the anesthetic nitrous oxide.

Neurotransmitters and Function: Monoamines - Serotonin

Helps control mood stability including depression and anxiety, appetite, sleep, and sexual activity. Many antidepressant drugs are aimed at increasing the amount of serotonin in the synaptic gaps by blocking their reabsorption, thus elevating mood.

Neurotransmitters and Function: Others - Corticotrophins (CRF, ACTH, cortisone)

Hormones that also function as neurotransmitters. CRF is produced by the hypothalamus in the brain and activates the pituitary gland to release ACTH during stress. CRF and ACTH induce an uncomfortable fight or flight response. ACTH then causes a release of cortisone by the adrenal glands that turn off the CRF and ACTH release to complete the human stress cycle. Aid in immune system, healing and stress control.

How are messages between neurons sent and received? Excitatory Neurotransmitters:

Increase cell firings.

How does heredity affect drug metabolism?

Individuals pass traits to their offspring that affect the metabolism of drugs.

Drug Processes that Alter Effects of Neurotransmitters: Inhibiting Enzyme Activity

Inhibit an enzyme that helps synthesize neurotransmitters to slow the nerve cells production of neurotransmitters. Also inhibit enzymes that metabolize neurotransmitters in the synaptic gap, thus increasing the number of active neurotransmitters.

Polydrug Abuse: Cycling

Intense use of a drug over a period of time, abstaining or using another drug to rest the body or to lower tolerance.

Drug Processes that Alter Effects of Neurotransmitters: Interfere with Re-uptake and Storage

Interfere with the reuptake and storage of neurotransmitters, allowing them to seep out of vesicles and become degraded, thus causing a shortage of those particular neurotransmitters.

Neurotransmitters and Function: Opioid Peptides - Endorphins, enkephalins, dynorphins, and opioid peptides

Involved in regulation of pain, the mitigation of stress (emotional and physical), the immune response, stomach functions, and a number of other physiological functions. Also, intimately involved in addiction pathway.

Polydrug Abuse: Switching

Involves using one drug in an abusive or addictive manner and then switching to another drug addiction.

How does gender affect drug metabolism?

Males and females have different body chemistries and different body water percentages.

Define: Half-life

Measure of the time it takes for half the dose to be inactivated or eliminated from the body.

Define: Explicit Memory

Memories stored at a conscious level.

Define: Implicit Memory

Memories stores at an unconscious level.

Building Blocks of Nervous System: Synaptic Gap or Cleft (synapse)

Microscopic gaps that exist between terminals of one nerve cell and an adjoining nerve cell.

Building Blocks of Nervous System: Neurotransmitters

Molecular bits of messenger chemicals that have been synthesized within the neuron From protein and molecules from whatever nutrients the body ingests. Stored in tiny sacs called vesicles that travel through the neuron to the axon terminals.

Define: Psychoactive Drugs

Natural, semisynthetic, and synthetic substances that directly affect the neurochemistry and anatomy of the central nervous system, causing mental, emotional and physical changes.

Type of Tolerance: Pharmacodynamic Tolerance

Nerve cells become less sensitive to the effects of a drug.

Building Blocks of Nervous System: Neuron

Nerve cells that are the building blocks of the nervous system

Building Blocks of Nervous System: Cell Body (soma)

Nourishes the cell and keeps it alive

Withdrawal: Nonpurposive

Objective physical signs such as seizures, sweating, goosebumps, vomiting, diarrhea and tremors depending on the drug.

Old Brain: Definition

Often called the primal or primitive brain, consists of the brainstem, cerebellum, and mesocortex (mid-brain) which contain the limbic system (emotional center). The old brain acts 4 or 5 times more rapidly than the new brain.

Drug Processes that Alter Effects of Neurotransmitters: Prevent Re-absorption (re-uptake)

Prevent neurotransmitters from being reabsorbed into the sending neuron, thereby causing them to remain in the synapse to slot into receptors again, inducing more intense effects.

Define: Blood-Brain Barrier

Protects the CNS. The walls of the capillaries of this barrier consist of tightly sealed epithelial cells that allow only certain substances to penetrate. Psychoactive drugs are able to penetrate the blood-brain barrier. The brain is essentially fat so fat-soluble substances can pass easily.

What do psychoactive drugs and neurotransmitters have in common? How are drugs and natural sensations opposite of one another?

Psychoactive drugs are similar to neurotransmitters because they mimic or disrupt naturally occurring chemicals in the brain and the body that have specific receptor sites. Psychoactive drugs cannot create sensations or feelings that do not already have a natural counterpart in the body.

Building Blocks of Nervous System: Dendrites

Receive signals from other nerve cells and relay them through the cell body

Building Blocks of Nervous System: Terminals

Relay messages to the dendrites, cell body, or terminals of the next nerve cell

What do researchers believe plays a more important role than euphoria or conscious memories in the development of the obsessive aspect of drug addiction? How are memories stored?

Researchers believe that implicit memories play a more important role than euphoria and explicit memories. Memories are solid bits of protein imprinted on the brain as microscopic memory bumps called Dendritic Spines.

Psychological Dependence: Social Reinforcement

Social factors encourage the continued use of an addictive psychoactive substance.

What does research show is the reason why some people are drawn to certain drugs?

Some people have an imbalance of one or more neurotransmitters and when they experiment with different substances, they discover that a specific drug or drugs help correct imbalance temporarily.

Psychological Dependence: Drug automatism

Substances such as sedatives and opiates can induce an aimless, unconscious, repetitive drug-taking behavior.

Polydrug Abuse: Stacking

Taking two or more similar drugs at one time to enhance a specific desired effect.

Key parts of the survival/reinforcement circuit in the brain:

The Nucleus Accumbens Septi (NAc) is the main part. The ventral tegmental area (VTA), lateral hypothamalus , and the amygdala also play important roles.

Important Processes That Give Clues for Addiction and Relapse: Synaptic Plasticity

The ability of a synapse to change in strength and function when that pathway is overused or underused, often as a result of the intake of psychoactive drugs, the practice of compulsive behaviors, or because of extreme stress.

Withdrawal: Definition

The bodies attempt to rebalance itself after cessation of prolonged use of a psychoactive drug or compulsive behavior.

Type of Tolerance: Select Tolerance

The body develops tolerance to mental and physical effects at different rates.

Define: Metabolism. Key Organ?

The body's mechanism for processing using and inactivating a foreign substance that has entered the body. Key metabolic organ is the liver.

Define: Bio-Availability

The degree to which the active ingredients of a drug become available to the target tissues after administration.

New Brain: Function

The new brain allows us to speak, reason, create, remember, make decisions, and then act. The old brain simply reacts.

How does age affect drug metabolism?

The older a person gets, the less liver produces fewer and fewer enzymes capable of metabolizing certain drugs. The older the person, the greater the effect. Usually starts after the age of 30.

Important Processes That Give Clues for Addiction and Relapse: Allostasis

The overall process of achieving and maintaining functionality by physiological and behavioral change.

Define: Excretion. Key Organ?

The process of eliminating the foreign substance that has entered the body. The kidneys are the primary excretory organs.

Define: Pharmacokinetics

The process through which the drug is absorbed, distributed, metabolized, eliminated & excreted by the body.

Withdrawal: Post-Acute/PAWS

The recurrent persistence of subtle yet significant emotional and psychological problems that can last for three to six months or (rarely) even longer into recovery and can trigger relapse.

How do psychoactive drugs affect memory bumps?

The stronger the psychoactive drug, the more rapid growth and proliferation of memory bumps and therefore the more deeply imprinted the memory.

Type of Tolerance: Reverse Tolerance

The user becomes more sensitive and therefore less able to handle even moderate amounts of the drug.

Define: Cross-Dependence

Tissue dependence on one drug creates dependence on other drugs.

Polydrug Abuse: Multiple Drug Use

Use of several drugs to attain different feelings.

Psychological Dependence: Definition

Users begin to rely on psychoactive drugs emotionally as well as physically.

Polydrug Abuse: Morphing

Using one drug to counteract the unwanted effects of another drug.

How many estimated nerve cells and connections do we have?

We have an estimated 100 billion nerve cells and about 100 trillion connections.

Routes of Administration: Inhalation

When a person smokes, vapes inhales a substance, the vaporized drug is rapidly absorbed through capillaries lining the air sacs (alveoli) of the bronchi (air passages). It takes approximately 7-10 seconds for the drug to reach the brain.

Define: Titration

When a user is able to continuously regulate the amount of drug they are receiving.

Define: Self-Medication

When a user takes a drug in an attempt to self-treat a physiological or physical trait.

Define: Blood-Cerebral Spinal Fluid Barrier

helps prevent unwanted substances from entering the areas of the CNS where the fluid flows.

Tolerance: Definition

if use continues over a long period of time, the body is forced to change and adapt. Larger and larger amounts must be taken to achieve the same effect. A user must cross a certain level of use for the development of tolerance to accelerate. Tolerance usually returns to normal once user stops taking the drug.

Define: Active Transport

occurs when fat-soluble (hydrophilic) drugs cross the blood-brain barrier by hitching a ride on protein molecules.

Define: Passive Transport

occurs when water-soluble drugs pass from an area where there is a higher concentration of a drug to an area of lower concentration.